Transient neonatal diabetes mellitus 1

Transient neonatal diabetes mellitus is caused by overexpression of a gene cluster at 6q24. These genes are paternally imprinted, so imprinting defects, duplications and ZFP57 mutations can cause such an overexpression. Patients develop abnormalities antenatally. The diabitis starts at one week of age and lasts for about 3 month.

Diabetes mellitus depelops with 1 week of age but hight blood glucose is measurable immediatly after birth. Initially the patient may require insulin, but after on average 6 month, this is no longer necessary and after about 18 month all abnormalities of glucose metabolism almost disappear. They may reappear in children during infections or in women during pregnancies. These patient more frequently develop type 2 diabetes.

Pathogenesis

40% of cases are caused by paternal uniparental disomy of chromosome 6 (UPD6). The same percentage is caused by paternal duplication of 6q24. About 20% are caused by hypomethylation of the maternal PLAGL1/HYMAI DMR. Half of the latter cases bear a pathogenetic mutation of the ZFP57 gene.

Diatloff-Zito C et al. (2007) Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region.